Enrollment of Black Americans in Pivotal Clinical Trials Supporting Food and Drug Administration (FDA) Chimeric Antigen Receptor (CAR)-T Cell Therapy Approval in Hematological Malignancies

INTRODUCTION

Black Americans are under-represented in clinical trials that supported FDA drug approvals of various hematological malignancies. (Al Hadidi et.al. Ann Intern Med 2020) CAR-T cell therapy, a new significant advancement in hematological malignancies, is currently approved for use in multiple myeloma (MM), acute lymphoblastic leukemia (ALL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and follicular lymphoma (FL). Enrollment of Blacks in clinical trials that supported those approvals are not well described.

METHODS

We conducted a retrospective analysis of 7 pivotal clinical trials that resulted in approval of of tisagenlecleucel for ALL in 2017, axicabtagene ciloleucel for DLBCL in 2017, tisagenlecleucel for DLBCL in 2018, brexucabtagene autoleucel for mantle cell lymphoma in 2020, lisocabtagene maraleucel for DLBCL in 2020, axicabtagene ciloleucel for follicular lymphoma in 2021 and idecabtagene vicleucel for multiple myeloma in 2021. Prevalence-corrected estimates for enrollment of Blacks were calculated as the percentage of Blacks among clinical trial participants divided by the percentage of Blacks in the disease population (participation to prevalence ratio [PPR]).A range between 0.8 and 1.2 reflects similar representation of Black Americans in the trial and disease population Data on drug products and demographic subgroups were extracted from Drugs@fda which include publically available data from the FDA.

RESULTS

Efficacy was reported in 74% (782 of 1051 patients) of enrolled patients across all the approved CAR-T products. Blacks constituted only 3.6% (28 of 782) of treated patients. Most treated patients had DLBCL (58%) or MM (16%). Two of seven studies (29%) didn't report ethnicity/race and/or included Blacks under others ethnic category. Blacks constituted only 4% of DLBCL patients, 6% of MM patients and 1% across other indications. Adjusted prevalence measures showed very low PPR in MM (0.17), a disease that is more common in Blacks and relatively better enrollment, though still sub-optimal, in DLBCL (PPR: 0.6).

CONCLUSIONS

Blacks are under-represented in clinical trials that supported CAR-T therapies for various hematological malignancies especially in MM. Efforts should be made to enroll more Blacks in clinical trials that include novel, potentially beneficial CAR-T products.